Lipid metabolism modulation is associated with molecular injury and kidney dysfunction in a rat ischemia model

ABSTRACT: Due to organ shortage, the transplantation community are increasingly using kidney from deceased donors such as donation after circulatory death (DCD) and donation after brain death (DBD). However, DCD donation have increased delayed graft function compared to DBD, an underline mechanism is still not well defied at the molecular level. In this study, we employed a rat model to mimic warm ischemia (45 mins) and reperfusion injury (IRI) for 4h and 24h. Apoptotic and tissue histological staining confirmed apoptosis and necrosis occurred at 4h and 24h post IRI respectively. Tissue proteome study revealed acute phase response, coagulation and complement activation and lipid X receptor activation as major pathway altered in intervention kidneys. Metabolomics follow up disclosed an increased level of lipids and fatty acids (FA). Mitochondrial function analysed by mitochondrial complex I activity and oxygen consumption and ATP levels in intervention kidney tissues were maintained 4h post IRI, but was significantly reduced 24h post IRI. Integrated proteo-metabolome analysis discovered an increased FA beta-oxidation 4h post IRI to sustain energy production. Kidney function were declined 24h post IRI indicated by increased blood creatinine and lactate levels. This study provides the frame work for the design of future metabolic intervention strategies to minimize kidney injury.

INSTRUMENT(S): Q Exactive HF

ORGANISM(S): Rattus Rattus (black Rat)

TISSUE(S): Kidney

SUBMITTER: Philip Charles  

LAB HEAD: Benedikt Kessler

PROVIDER: PXD005101 | Pride | 2020-07-06

REPOSITORIES: Pride